Defective regulatory volume decrease in human cystic fibrosis tracheal cells because of altered regulation of intermediate conductance Ca2+-dependent potassium channels

The cystic fibrosis transmembrane conductance regulator (CFTR) protein has the ability to function as both a chloride channel and a channel regulator. The loss of these functions explains many of the manifestations of the cystic fibrosis disease (CF), including lung and pancreatic failure, meconium ileus, and male infertility. CFTR has previously been implicated in the cell regulatory volume decrease (RVD) response after hypotonic shocks in murine small intestine crypts, an effect associated to the dysfunction of an unknown swelling-activated potassium conductance. In the present study, we investigated the RVD response in human tracheal CF epithelium and the nature of the volume-sensitive potassium channel affected. Neither the human tracheal cell line CFT1, expressing the mutant CFTR-ΔF508 gene, nor the isogenic vector control line CFT1-LC3, engineered to express the βgal gene, showed RVD. On the other hand, the cell line CFT1-LCFSN, engineered to express the wild-type CFTR gene, presented a full RVD. Patch-clamp studies of swelling-activated potassium currents in the three cell lines revealed that all of them possess a potassium current with the biophysical and pharmacological fingerprints of the intermediate conductance Ca2+-dependent potassium channel (IK, also known as KCNN4). However, only CFT1-LCFSN cells showed an increase in IK currents in response to hypotonic challenges. Although the identification of the molecular mechanism relating CFTR to the hIK channel remains to be solved, these data offer new evidence on the complex integration of CFTR in the cells where it is expressed.

Intermediate- and long-term earthquake prediction.

Progress in long- and intermediate-term earthquake prediction is reviewed emphasizing results from California. Earthquake prediction as a scientific discipline is still in its infancy. Probabilistic estimates that segments of several faults in California will be the sites of large shocks in the next 30 years are now generally accepted and widely used. Several examples are presented of changes in rates of moderate-size earthquakes and seismic moment release on time scales of a few to 30 years that occurred prior to large shocks. A distinction is made between large earthquakes that rupture the entire downdip width of the outer brittle part of the earth's crust and small shocks that do not. Large events occur quasi-periodically in time along a fault segment and happen much more often than predicted from the rates of small shocks along that segment. I am moderately optimistic about improving predictions of large events for time scales of a few to 30 years although little work of that type is currently underway in the United States. Precursory effects, like the changes in stress they reflect, should be examined from a tensorial rather than a scalar perspective. A broad pattern of increased numbers of moderate-size shocks in southern California since 1986 resembles the pattern in the 25 years before the great 1906 earthquake. Since it may be a long-term precursor to a great event on the southern San Andreas fault, that area deserves detailed intensified study.

Morphology of high-luminosity compact radio sources.

High-dynamic range imaging and monitoring with very-long-baseline interferometry reveal a rich morphology of luminous flat-spectrum radio sources. One-sided core-jet structures abound, and superluminal motion is frequently measured. In a few cases, both distinct moving features and diffuse underlying jet emission can be detected. Superluminal motion seen in such sources is typically complex, on curved trajectories or ridge lines, and with variable component velocities, including stationary features. The curved trajectories seen can be modeled by helical motion within the underlying jet flow. The very-long-baseline interferometry properties of the superluminal features in the jet of 3C 345 and other similar sources can be explained by models invoking the emission from shocks, at least within the vicinity of the compact core. Inverse-Compton calculations, constrained by x-ray observations, yield realistic estimates for the physical conditions in the parsec-scale jet. There is evidence for a transition region in this source beyond which other factors (e.g., plasma interactions and nonsynchrotron radiation processes) may become prominent. Multifrequency and polarization imaging (especially at high frequencies) are emerging as critical tools in testing model predictions.

The acceleration and collimation of jets.

I will discuss several issues related to the acceleration, collimation, and propagation of jets from active galactic nuclei. Hydromagnetic stresses provide the best bet for both accelerating relativistic flows and providing a certain amount of initial collimation. However, there are limits to how much "self-collimation" can be achieved without the help of an external pressurized medium. Moreover, existing models, which postulate highly organized poloidal flux near the base of the flow, are probably unrealistic. Instead, a large fraction of the magnetic energy may reside in highly disorganized "chaotic" fields. Such a field can also accelerate the flow to relativistic speeds, in some cases with greater efficiency than highly organized fields, but at the expense of self-collimation. The observational interpretation of jet physics is still hampered by a dearth of unambiguous diagnostics. Propagating disturbances in flows, such as the oblique shocks that may constitute the kiloparsec-scale "knots" in the M87 jet, may provide a wide range of untapped diagnostics for jet properties.